Chloroethylene

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline study, published in peer-reviewed literature, minor restrictions in design and reporting, but otherwise adequate for assessment.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Mutagenicity of vinyl chloride, vinylidene chloride and chloroprene in V79 Chinese hamster cells.

Author:

Drevon C, Turoki T

Year:

1979

Bibliographic source:

Mut Res 67:173-182

Reference 2

Reference Type:

publication

Title:

Microsome-mediated mutagenesis of a Chinese hamster cell line by various chemicals.

Author:

Drevon, C.; Kuroki, T.; Montesano, R.

Year:

1978

Bibliographic source:

Mutat. Res. 53:181-182

Materials and methods

Principles of method if other than guideline:

Mammalian cell gene mutation assay in Chinese hamster cells

GLP compliance:

no

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Chloroethylene

EC Number:

200-831-0

EC Name:

Chloroethylene

Cas Number:

75-01-4

Molecular formula:

C2H3Cl

IUPAC Name:

chloroethene

Details on test material:

Vinyl chloride (purity 99.9%) contaminated with ethanol (30 ppm), water (20 ppm), methyl chloride (< 20 ppm) and non-volatile substances (< 5 ppm)
was tested

Method

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

S15 post-mitochondrial fraction from livers of BDVI or OF-1 male rats treated with phenobarbitone (1 mg/ml) in drinking water for 7 days

Test concentrations with justification for top dose:

0, 5, 10, 20 or 30% v/v in atmosphere

Vehicle / solvent:

Air

Controls

Untreated negative controls:

other: yes, but type of controls not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

Cells (1.5 x 10*E6/plate) were incubated (in liquid suspension or 0.3% agar) with 0.75 ml S15 post-mitochondrial fraction from livers of BDVI or
OF-1 male rats that had been treated with phenobarbitone (1 mg/ml) in drinking water for 7 days in the presence or absence of an NADPH-generating
system. Plates were placed in an evacuated dessicator and exposed to 0, 5, 10, 20 or 30% v/v vinyl chloride. Additional plates were exposed to vinylidene chloride or chloroprene. Pressure was adjusted to atmospheric after 20-30 min. After exposure for 5, 10 or 15 hr (37 degrees C), vapor was removed under vacuum and replaced by air, cells were washed twice, and fresh medium was added. Cytotoxicity was determined by culturing 100 treated cells/dish for 7 days. Cells to be used in mutagenesis assays were plated at 2 x 10 *E4 and 10 *E5 cells per dish. After an expression period of 48 hr, 20 micrograms/ml 8-azaguanine (AZA) or 1mM ouabain (OUA) were added to the culture medium. Media were changed after 5-7 days. Cultures were fixed and stained with Giemsa after 12 and 14 days treatment with AZA or OUA, respectively

Evaluation criteria:

No data

Statistics:

No data

Results and discussion

Test results

Test results 1

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

other: yes, but type of controls not specified

Positive controls validity:

not specified

Test results 2

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

other: yes, but type of controls is not specified

Positive controls validity:

not specified

Additional information on results:

An increased rate of mutation or cytotoxicity over controls was not observed in cells exposed to vinyl chloride in the absence of S15.

In cells suspended in liquid or agar containing S15 from phenobarbitone pretreated rats, exposure to 20% vinyl chloride induced a maximal mutation rate of 30% and 3% in AZA and OUA resistance, respectively. Maximal rates of mutation were observed at 5 hr in liquid incubation and 10-15 h in agar
incubation. The mutation and survival rates of cells in liquid suspension that were treated with vinyl chloride (5-30 %) for 5 hours were dose dependent. The mutation frequencies of cells exposed to 30% (51 AZA and 4 OUA resistant colonies) were 10-20 times greater than spontaneous
rates . The percent survival of cells treated with 0, 5, 20 or 30% vinyl chloride for 5 hours was 100%, 90%, 70% and 50%, respectively.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.